JHEP Reports (Jan 2025)
Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy
- Tingyan Wang,
- Cori Campbell,
- Alexander J. Stockdale,
- Stacy Todd,
- Karl McIntyre,
- Andrew Frankland,
- Jakub Jaworski,
- Ben Glampson,
- Dimitri Papadimitriou,
- Luca Mercuri,
- Erik Mayer,
- Christopher R. Jones,
- Hizni Salih,
- Gail Roadknight,
- Stephanie Little,
- Theresa Noble,
- Kinga A. Várnai,
- Cai Davis,
- Ashley I. Heinson,
- Michael George,
- Florina Borca,
- Louise English,
- Luis Romão,
- David Ramlakhan,
- Kerrie Woods,
- Jim Davies,
- Eleni Nastouli,
- Salim I. Khakoo,
- William Gelson,
- Graham S. Cooke,
- Eleanor Barnes,
- Philippa C. Matthews,
- Eleanor Barnes,
- Philippa C. Matthews,
- William Gelson,
- Graham S. Cooke,
- Salim I. Khakoo,
- Eleni Nastouli,
- Jim Davies,
- Kerrie Woods,
- Alexander J. Stockdale,
- Stephen Ryder,
- Ahmed Elsharkawy,
- Nicholas Easom,
- William Bernal,
- Shazaad Ahmad,
- Douglas Macdonald,
- Tingyan Wang,
- Cori Campbell,
- Simon Stanworth,
- Suzanne Maynard,
- Gail Roadknight,
- Stephanie Little,
- Kinga A. Várnai,
- Ben Glampson,
- Dimitri Papadimitriou,
- Luca Mercuri,
- Christopher R. Jones,
- Jakub Jaworski,
- Cai Davis,
- Florina Borca,
- Ashley Heinson,
- Michael George,
- Heidi MacNaughton,
- Yun Kim,
- Josune Olza Meneses,
- Louise English,
- Timothy Roberts,
- Luis Romão,
- David Ramlakhan,
- Stacy Todd,
- Heather Rogers,
- Karl McIntyre,
- Andrew Frankland,
- Hizni Salih,
- Theresa Noble,
- Lara Roberts,
- Finola Higgins,
- Javier Vilar,
- Ruth Norris,
- George Tilston,
- Ilina Serafimova,
- Sarah Montague,
- Juliette Verheyden,
- Irene Juurlink,
- Kathryn Jack,
- Alex Waldren-Glenn,
- Lizzie Poole,
- Victoria Day,
- Berit Reglar
Affiliations
- Tingyan Wang
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Cori Campbell
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Alexander J. Stockdale
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical Infectious Diseases Unit, Royal Liverpool Hospital, Liverpool University Hospitals NHS Trust, Liverpool, UK
- Stacy Todd
- Tropical Infectious Diseases Unit, Royal Liverpool Hospital, Liverpool University Hospitals NHS Trust, Liverpool, UK
- Karl McIntyre
- Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Trust, Liverpool, UK
- Andrew Frankland
- Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Trust, Liverpool, UK
- Jakub Jaworski
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Ben Glampson
- iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, London, UK
- Dimitri Papadimitriou
- iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, London, UK
- Luca Mercuri
- iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, London, UK
- Erik Mayer
- iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, London, UK
- Christopher R. Jones
- Department of Surgery and Cancer, Imperial College London, London, UK; Department of Infectious Disease, Imperial College London, London, UK
- Hizni Salih
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Gail Roadknight
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Stephanie Little
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Theresa Noble
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Kinga A. Várnai
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Cai Davis
- Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
- Ashley I. Heinson
- Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
- Michael George
- Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
- Florina Borca
- Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
- Louise English
- NIHR University College London Hospitals Biomedical Research Centre, London, UK
- Luis Romão
- NIHR University College London Hospitals Biomedical Research Centre, London, UK
- David Ramlakhan
- NIHR University College London Hospitals Biomedical Research Centre, London, UK
- Kerrie Woods
- NIHR Oxford Biomedical Research Centre, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Jim Davies
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Computer Science, University of Oxford, Oxford, UK
- Eleni Nastouli
- Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Virology, UCLH, London, UK
- Salim I. Khakoo
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- William Gelson
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Graham S. Cooke
- iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Cancer, Imperial College London, London, UK; Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK
- Eleanor Barnes
- NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Corresponding authors. Address: The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. Tel.: +44-1865-281547 (E. Barnes); The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK (P.C. Matthews).
- Philippa C. Matthews
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; The Francis Crick Institute, London, UK; Division of Infection and Immunity, University College London, London, UK; Department of Infectious Diseases, University College London Hospital, London, UK; Corresponding authors. Address: The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. Tel.: +44-1865-281547 (E. Barnes); The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK (P.C. Matthews).
- Eleanor Barnes
- Philippa C. Matthews
- William Gelson
- Graham S. Cooke
- Salim I. Khakoo
- Eleni Nastouli
- Jim Davies
- Kerrie Woods
- Alexander J. Stockdale
- Stephen Ryder
- Ahmed Elsharkawy
- Nicholas Easom
- William Bernal
- Shazaad Ahmad
- Douglas Macdonald
- Tingyan Wang
- Cori Campbell
- Simon Stanworth
- Suzanne Maynard
- Gail Roadknight
- Stephanie Little
- Kinga A. Várnai
- Ben Glampson
- Dimitri Papadimitriou
- Luca Mercuri
- Christopher R. Jones
- Jakub Jaworski
- Cai Davis
- Florina Borca
- Ashley Heinson
- Michael George
- Heidi MacNaughton
- Yun Kim
- Josune Olza Meneses
- Louise English
- Timothy Roberts
- Luis Romão
- David Ramlakhan
- Stacy Todd
- Heather Rogers
- Karl McIntyre
- Andrew Frankland
- Hizni Salih
- Theresa Noble
- Lara Roberts
- Finola Higgins
- Javier Vilar
- Ruth Norris
- George Tilston
- Ilina Serafimova
- Sarah Montague
- Juliette Verheyden
- Irene Juurlink
- Kathryn Jack
- Alex Waldren-Glenn
- Lizzie Poole
- Victoria Day
- Berit Reglar
- Journal volume & issue
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Vol. 7,
no. 1
p. 101229
Abstract
Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes. Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase, and with liver fibrosis/cirrhosis. Results: We retrieved data from 1,885 adults on NA treatment (median follow-up 6.2 years, IQR 3.7–9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5–17). Five VL classes were identified from the derivation cohort (n = 1,367, discrimination: 0.93, entropy: 0.90): class 1 ‘long term suppression’ (n = 827, 60.5%), class 2 ‘timely virological suppression’ (n = 254, 18.6%), class 3 ‘persistent moderate viraemia’ (n = 140, 10.2%), class 4 ‘persistent high-level viraemia’ (n = 44, 3.2%), and class 5 ‘slow virological suppression’ (n = 102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n = 518). Alanine transaminase decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p <0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had twofold increased hazards of fibrosis/cirrhosis compared with class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33–3.02). Conclusions: Heterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression. Impact and implications: Treatment recommendations for people living with chronic hepatitis B virus (HBV) infection are becoming less stringent, meaning that more of the population will be eligible to receive therapy with nucleos(t)ide analogue agents. We explored outcomes of HBV treatment in a large UK dataset, describing different responses to treatment, and showing that the viral load is not completely suppressed after 1 year in about one in five cases, associated with an increased risk of liver complications. As treatment is rolled out more widely, patients and clinicians need to be aware of the potential for incomplete virologic responses. The findings can support the identification of high-risk individuals, improve early fibrosis and cirrhosis prediction, guide monitoring and preventive interventions, and support public health elimination goals.
